The future is never obvious, even if we live for decades as if it were, but there are people who are very aware of it. After a diagnosis, a cancer patient may see time thicken and begin to behave in a paradoxical manner. It can feel like months of days waiting for results or when your body aches, yet time becomes scarce. Vital decisions are reviewed with anguish and previously unthinkable possibilities begin to be contemplated. This also happens to professional investors, that guild of futurists in which a few earn a lot because the majority are wrong.
This weekend, these two groups of people look at Madrid with hope and anxiety. More than 7,000 people gathered this Saturday to listen to the presidential symposium of the congress of the European Society of Medical Oncology (ESMO), whose star moment was the presentation of the results of INTerpath-001, a clinical trial on a personalized vaccine against melanoma that has given a lot of talk since August.
The presentation was given by Georgina Long, medical director of the Melanoma Institute Australia and head of Medical Oncology and Translational Research at the University of Sydney. In August, pharmaceutical companies Merck and Moderna announced that the Phase III trial of their experimental treatment had achieved significant and clinically relevant reductions in tumor recurrence. The news fueled hopes for a new class of cancer treatments and multiplied the companies' stock market value.
The detailed results confirm the benefit, although they also help to define its scope. In a trial of 1,137 patients with high-risk cutaneous melanoma, completely removed by surgery, adding a personalized messenger RNA vaccine—autogeneous intismeran—to treatment with the antibody pembrolizumab reduced the risk of relapse or death by 42%, compared to administering the latter drug alone. At two years, 82.2% of patients who had received the combination remained recurrence-free, compared to 70% of those who received pembrolizumab alone.
The improvement is relevant in a disease that can reappear after surgery and spread to other organs, but it still does not allow us to know how many additional years of life the treatment could provide. As Long explained in his presentation, the overall survival data are not yet mature and the trial continues.
The combination also reduced the risk of developing distant metastases or dying by 38%. At two years, 88.5% of patients who had received the vaccine together with pembrolizumab had not suffered distant metastasis, compared to 80.2% of the group treated with the antibody alone. This result matters because the spread of melanoma to other organs is one of the factors that worsens the prognosis of patients.
The presentation comes after a week with important movements in the markets associated with the expectations placed on the new treatment. On Thursday, the leak of the results that were going to be presented at ESMO caused a sharp drop in the shares of the two pharmaceutical companies. Moderna lost 26% and Merck fell 3.9%, in a day that erased billions of dollars in stock market value. In the case of Moderna, which lost $24 billion in valuation, the setback halted a spectacular rise in its shares, of more than 500% so far this year.
The figures show the distance that can separate financial expectations from clinical results. Investors hoped that the personalized vaccine would become a new source of income for companies, but the announcement of a positive result does not guarantee that the business will meet all forecasts.
In statements reported by Reuters, UBS analyst Michael Yee described the relapse-free survival results as “solid data” and attributed part of the stock market reaction to the “sell on the news” strategy: buying when favorable rumors circulate and selling when the reality is known, especially if previous expectations were very high.
An earlier phase of the trial, with fewer patients and different follow-up, had shown a 49% reduction in the risk of relapse or death and a 59% reduction in the risk of distant metastasis or death. The percentages in the new study are lower, but the differences between the populations analyzed and the follow-up periods prevent direct comparison of the results.
The phase III trial provides broader, more robust evidence that the combination can benefit patients with resected melanoma, but it does not prove that the therapy will have the same effect in other cancers or that it will become a universal treatment.
Some researchers have welcomed the data as a breakthrough for immunotherapy. “We are facing a new frontier,” said Karen Knudsen, executive director of the Parker Institute, an institution that helps fund cancer immunotherapy research. Michael Atkins, deputy director of the Lombardi Comprehensive Cancer Center at Georgetown University, has noted that “it is a great advance for science and oncology, because this vaccine can be applied to many different types of cancer.”
The possibility of extending this strategy to other tumors is one of the reasons why the trial has attracted so much attention. Merck and Moderna are already investigating the same technology in other types of cancer, including lung, bladder and kidney cancer. But the result in melanoma does not allow us to anticipate the outcome of these studies. Each tumor accumulates different mutations and develops its own strategies to escape the immune system. A therapy that works in one context may not work in another.
The logic of the treatment consists of teaching the body's defenses to recognize the particular characteristics of a tumor. After surgical removal, a sample of the cancer is analyzed and mutations that produce abnormal proteins, known as neoantigens, are identified. With this information, a messenger RNA (mRNA) vaccine is designed that contains the instructions to produce up to 34 of these neoantigens. Once administered, the patient's cells make the proteins and present them to the immune system, which can learn to recognize the cancer cells that contain them if the disease returns.
Pembrolizumab acts through another complementary route. This antibody blocks the PD-1 protein, a kind of molecular brake on T lymphocytes, the immune cells that can attack cancer. The vaccine helps guide the response towards the characteristics of the tumor and pembrolizumab makes it difficult for it to stop the action of the defenses. The combination seeks to teach the immune system where to attack and make it easier for it to maintain the attack.
Although there is talk of a vaccine against cancer, this therapy does not work like preventive vaccines that are administered to large groups of the population. There are already vaccines of this type against cancer. Those that protect against human papillomavirus and hepatitis B prevent infections that can cause cancer. Intismeran, on the other hand, is an individualized therapy that is prepared for a person whose tumor has already appeared and been removed. It is not mass-produced so that it serves everyone in the same way because its design depends on the mutations found in each cancer.
The INTerpath-001 trial studied patients with completely resected high-risk stage IIB to IV cutaneous melanoma. The combination is given after surgery, in a setting known as an adjuvant, with the intention of eliminating cancer cells that may have remained in the body and reducing the chance of the disease returning. The results do not show that the vaccine works in patients with tumors that continue to grow or with metastases that cannot be removed. Nor do they allow us to affirm that it will benefit all patients with melanoma.
Research on personalized cancer vaccines has spent years trying to turn a promising idea into a demonstrable clinical improvement. Long recalled the previous attempts and posed a question that summarizes the dimension of the result: “How do we get here today, in 2026, to see success in individualized therapy for the first time?” His response paid tribute to “more than 100 years of discovery and work in cancer biology, cancer immunology, and the development of innovative technologies.”
The trial provides important evidence that such a strategy can work in certain circumstances. It remains to be seen whether the reduction in relapses will translate into longer survival, how long the benefit will last, and what role the treatment will have in other tumors. For pharmaceutical companies, the answers will also determine the commercial value of the technology, but for patients, the question is more immediate and less abstract. After an operation, each month without the disease recurring can be a lifetime, but it is still necessary to find out how much survival time the new treatment provides.
